The allosteric regulation of enzyme activity is fundamental to preventing metabolic and homeostatic chaos. A colossal number of complex, multifunctional enzymes important to metabolic and cellular processes exhibit some form of dynamic regulation. Cellular respiration in the mitochondria of higher organisms is paramount to supplying the ATP needed to sustain biological processes. The redox reactions of the mitochondrial respiratory chain, which consists of four transmembrane enzyme complexes, a lipid-soluble electron carrier (ubiquinone), and a water-soluble electron carrier (cytochrome c), generate the electrochemical proton gradient necessary to drive ATP synthesis. While ample evidence has shown that these enzymes exist as both solitary units and supercomplex assemblies in the inner mitochondrial membrane, controversy surrounds the functional and kinetic advantage gained by the formation of the mutli-enzyme supercomplexes. Our most exciting project involves answering the simple question “How do mitochondrial respiratory proteins work?”

Students will use site-directed mutagenesis to manipulate residues within the protein and characterize the regulation of these mutants using chemical biology and enzymology, include protein engineering, site-directed mutagenesis, steady-state and pre-steady-state kinetics, organic synthesis, bioconjugate chemistry, ELISA and FRET.

Qualifications

Requirements: General Chemistry (2 semesters or equivalent), General Biology

Class or level of student sought: sophomore or higher

Needed skills: basic calculations of solution concentration, ability to use balance and volumetric flasks, ability to work in a group and independently

Additional requirements, if any: students will be expected to participate in group meetings (if schedule permits) and present at research and creative week.

Preferences: students with strong chemistry background or who have had organic chemistry/analytical chemistry will be given preference